The objective of this project is to determine whether topiramate slows disease progression in patients with amyotrophic lateral sclerosis (ALS). ALS is a progressive uniformly lethal neurodegerative disorder for which there is no known cure. Recent genetic and biochemical studies implicate glutamate excitotoxicity, free radical toxicity, and mitochondrial dysfunction as possible causes of familial ALS (FALS) and sporadic ALS (SALS) (1-10). Topiramate is a FDA approved agent for epilepsy. One mechanism of action of topiramate is to antagonize kainate activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamatergic excitatory amino acid receptor.